Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials.
Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes.
Design, Setting, And Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021.
Exposures: TBI.
Main Outcomes And Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ).
Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34).
Conclusions And Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.
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http://dx.doi.org/10.1001/jamanetworkopen.2021.3467 | DOI Listing |
Mol Cell Endocrinol
January 2025
This study investigated the consequences of perinatal exposure to Aroclor 1221 (A1221), a weakly estrogenic polychlorinated biphenyl (PCB) mixture and known endocrine-disrupting chemical (EDC), in female rats. Previous work has shown behavioral and physiological effects of A1221, and the current study extended this work to comprehensive transcriptomic profiling of two hypothalamic regions involved in the control of reproduction: the arcuate nucleus (ARC) and anteroventral periventricular nucleus (AVPV). Female Sprague-Dawley rats were fed a cookie treated with a small volume of A1221 (1 mg/kg) or vehicle (3% DMSO in sesame oil) during pregnancy from gestational days 8-18 and after birth from postnatal (P) days 1-21, exposing the offspring via placental and lactational transfer.
View Article and Find Full Text PDFJ Neurosci
January 2025
Neuroapoptosis Laboratory, Department of Neurological Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213;
Huntington's disease (HD), a neurodegenerative disease, affects approximately 30,000 people in the United States, with 200,000 more at risk. Mitochondrial dysfunction caused by mutant huntingtin (mHTT) drives early HD pathophysiology. mHTT binds the translocase of mitochondrial inner membrane (TIM23) complex, inhibiting mitochondrial protein import and altering the mitochondrial proteome.
View Article and Find Full Text PDFAdv Neonatal Care
December 2024
Author Affiliations: Department of Family and Community Health Nursing, Marcella Niehoff School of Nursing, Loyola University Chicago, Maywood, Illinois (Drs Griffith, and Tell, Mrs Ford, and Dr Janusek); Department of Internal Medicine, Division of Infectious Disease, Rush University, Chicago, Illinois (Dr Green); Division of Neonatology, Loyola University Medical Center, Maywood, Illinois (Mr Bohan, Mrs Grunwaldt, and Dr Amin); Nursing Research, Children's Wisconsin, Milwaukee, Wisconsin (Dr White-Traut); and Women, Children and Family Health Science, College of Nursing, University of Illinois at Chicago, Chicago, Illinois (Dr White-Traut).
Background: Early life stress exposure in preterm infants may alter DNA methylation of NR3C1 and HSD11B2, disrupting neurobehaviors needed for oral feeding (PO) skill development.
Purpose: To (1) examine the feasibility of the study protocol; (2) describe early life stress, DNA methylation of NR3C1 and HSD11B2, and PO skill development; and (3) explore the association between DNA methylation of NR3C1 and HSD11B2 and infant characteristics, early life stress, and PO skill development.
Method: We employed a longitudinal descriptive pilot study (N = 10).
CNS Neurosci Ther
December 2024
Department of Neurology, Mental and Neurological Disease Research Center, the Third Affiliated Hospital of Sun Yat-sen University, Guangzhou, China.
Background: Monocyte-derived macrophages and microglia initially adopt an anti-inflammatory phenotype following stroke but later transition to a pro-inflammatory state. The mechanisms underlying this phenotypic shift remain unclear. This study investigates the activation dynamics of molecular signaling pathways in macrophages and microglia after stroke.
View Article and Find Full Text PDFFront Pharmacol
November 2024
Department of Neurosurgery, The Second Hospital of Hebei Medical University, Shijiazhuang, China.
Objectives: The disruption of blood-brain barrier (BBB) is associated with poor outcomes of TBI patients. Sphingosine-1-phosphate receptor 2 (S1pr2), a member of the G protein-coupled receptor family, is involved in endothelial activation and the regulation of vascular integrity. We hypothesized that the inhibition of S1pr2 may alleviate BBB disruption and explored potential underlying molecular mechanisms.
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